Ovarian Cancer

Ovarian cancer is a group of malignancies arising in or near the ovary and fallopian tube, dominated by epithelial carcinomas. It is often detected at an advanced stage because early disease tends to be asymptomatic and no effective screening test exists, which contributes to its relatively high mortality among gynecologic cancers.

Definition

Ovarian cancer is a malignant neoplasm of the ovary, fallopian tube, or peritoneum, most commonly epithelial carcinoma (notably high-grade serous carcinoma), with less common germ-cell and sex-cord stromal tumors.

Scope

This entry covers the major histologic subtypes of ovarian cancer (with emphasis on high-grade serous carcinoma), the now-recognized fallopian-tube origin of many serous tumors, hereditary contributions through BRCA1/2 and homologous-recombination deficiency, and why the disease typically presents late. It is reference material, not individualized clinical guidance.

Core questions

• What are the principal subtypes of ovarian cancer and how do they differ in origin and behavior?
• Why are many high-grade serous cancers now thought to originate in the fallopian tube?
• How do BRCA1/2 mutations and homologous-recombination deficiency drive risk and treatment response?
• Why is ovarian cancer usually diagnosed at an advanced stage?

Key concepts

• High-grade serous carcinoma
• Fallopian-tube (tubal) origin hypothesis
• BRCA1/2 and hereditary breast-ovarian cancer syndrome
• Homologous-recombination deficiency
• PARP inhibition and synthetic lethality
• Absence of effective screening
• Advanced-stage presentation and peritoneal spread

Mechanisms

The most lethal and common form, high-grade serous carcinoma, is now thought in many cases to originate from precursor lesions in the fimbrial end of the fallopian tube rather than the ovarian surface itself. A substantial fraction of these cancers carry defects in homologous-recombination DNA repair, often through germline or somatic BRCA1/2 mutations; the identification of BRCA1 as a susceptibility gene (Miki, 1994) established the genetic basis of hereditary breast-ovarian cancer. Homologous-recombination deficiency underlies the synthetic-lethal vulnerability exploited by PARP inhibitors, which improve outcomes as maintenance therapy in newly diagnosed BRCA-mutated disease (Moore, 2018). Other subtypes (clear-cell, endometrioid, mucinous, germ-cell, sex-cord stromal) have distinct origins and behaviors (Lheureux, 2019).

Clinical relevance

Ovarian cancer's tendency to present late, combined with the lack of an effective screening test, shapes its clinical and research priorities, while the BRCA/homologous-recombination axis has made it a model for genetically targeted therapy. This entry describes these features for reference and is not a basis for individualized diagnosis or treatment.

Epidemiology

Ovarian cancer is less common than endometrial cancer but causes a disproportionate share of gynecologic-cancer deaths because of late detection (Bray, 2024). Risk is increased by family history and inherited BRCA1/2 mutations and by factors that increase lifetime ovulation, while parity, breastfeeding, and combined oral contraceptive use are associated with lower risk (Lheureux, 2019).

History

The cloning of BRCA1 (Miki, 1994) and subsequently BRCA2 transformed understanding of inherited ovarian cancer risk. Over the following decades, pathologic studies relocated the likely origin of many high-grade serous cancers to the fallopian tube, and the recognition of homologous-recombination deficiency led to PARP inhibitors and a precision-medicine era for the disease (Moore, 2018; Lheureux, 2019).

Debates

Screening for ovarian cancer

Despite large trials of approaches combining serum markers and ultrasound, no strategy has reliably reduced ovarian-cancer mortality in the general population, so routine screening of average-risk individuals is generally not recommended; the search for effective early detection continues.

Key figures

• Yoshio Miki
• Mark Skolnick
• Kathleen Moore
• Stephanie Lheureux

Seminal works

• miki-1994
• moore-2018
• lheureux-2019

Frequently asked questions

Is there a screening test for ovarian cancer?

No screening test has been shown to reliably reduce ovarian-cancer deaths in average-risk individuals, which is one reason the disease is often diagnosed at an advanced stage.

How do BRCA mutations relate to ovarian cancer?

Inherited BRCA1 or BRCA2 mutations substantially raise lifetime ovarian-cancer risk and impair DNA repair; the resulting homologous-recombination deficiency also makes such cancers more responsive to PARP-inhibitor therapy.